Treatment of Cushing Disease With Pituitary-Targeting Seliciclib
Authors' conclusion
Seliciclib may directly target pituitary corticotrophs in CD and reverse hypercortisolism. Potential liver toxicity of seliciclib resolves with treatment withdrawal. The lowest effective dose requires further determination.
Study context
- Population
- Adults with de novo, persistent, or recurrent Cushing disease (CD)9 treated
- Participants
- 16 adults
- Outcome
- Single-centre study: normalization of 24-hour UFC (≤ 50 µg/24 hours); multicentre study: UFC normalization or ≥ 50% reduction in UFC from baseline
- Follow-up
- Study end
Methodological detailsproof-of-concept single-centre and pilot multicentre, open-label, tertiary referral pituitary centre
- Proof-of-concept single-centre and pilot multicentre
- Open-label
- Tertiary referral pituitary centre
Main finding
As reported in the abstract
UFC normalization or ≥ 50% UFC reduction
Patients achieving ≥ 50% urinary free cortisol (UFC) reduction (range, 55%-75%)
3
Patients with 48% UFC reduction
2
Patients achieving UFC normalization
0
Observational data: associations, not effects.
Further findings
Mean UFC · baseline to study end
- Baseline mean UFC (± µg/24 hours)
- 226.4 ± 140.3 µg/24 hours
- Study-end mean UFC
- 131.3 ± 114.3 µg/24 hours
- Mean UFC decreased by 42%
- Longitudinal model: significant UFC reductions from baseline to each treatment week
Plasma adrenocorticotrophic hormone (ACTH) in patients with ≥ 48% UFC reduction
- Plasma ACTH decrease (P = 0.01)
- 19%
Safety
Patients
- Grade ≤ 2 elevated liver enzymes, anemia, and/or elevated creatinine, resolved with dose interruption/reduction
- 3
- Grade 4 liver-related serious adverse events, resolved within 4 weeks of discontinuation
- 2
Original publication
Treatment of Cushing Disease With Pituitary-Targeting Seliciclib. J Clin Endocrinol Metab. Published 10 October 2022. doi:10.
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